1. Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
2. State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
3. Department of Pharmacy, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
# Co-first authors, these two authors contributed equally to this work.
Excessive stress leads to disruptions of the central nervous system. Individuals' responses to stress and trauma differ from person to person. Some may develop various neuropsychiatric disorders, such as post-traumatic stress disorder, major depression, and anxiety disorders, while others may successfully adapt to the same stressful events. These two neural phenotypes are called susceptibility and resilience. Previous studies have suggested resilience/susceptibility as a complex, non-specific systemic response involving central and peripheral systems. Emerging research of mechanisms underlying resilience is mostly focussing on the physiological adaptation of specific brain circuits, neurovascular impairment of the blood-brain barrier, the role of innate and adaptive factors of the immune system, and the dysbiosis of gut microbiota. In accordance with the microbiota-gut-brain axis hypothesis, the gut microbiome directly influences the interface between the brain and the periphery to affect neuronal function. This review explored several up-to-date studies on the role of gut microbiota implicated in stressful events-related resilience/susceptibility. We mainly focus on the changes in behavior and neuroimaging characteristics, involved brain regions and circuits, the blood-brain barrier, the immune system, and epigenetic modifications, which contribute to stress-induced resilience and susceptibility. The perspective of the gut-brain axis could help to understand the mechanisms underlying resilience and the discovery of biomarkers may lead to new research directions and therapeutic interventions for stress-induced neuropsychiatric disorders.
Keywords: resilience, brain circuits, blood-brain barrier, immune system, epigenetics, gut microbiota